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MHRP Scientists and Collaborators Detect Declining Trend in Transmitted Drug Resistance in Acute HIV Infection Cohort

November 3, 2016
Prevalence among cohort has fallen below WHO low-level guideline

A recent study conducted by researchers from the U.S. Military HIV Research Program (MHRP) and the Thai Red Cross has shown that the prevalence of transmitted drug resistance (TDR) has declined in a cohort of individuals with acute HIV infection in Bangkok, Thailand. Findings were published earlier this week in the Journal of the International AIDS Society.

Drug resistant HIV can arise when HIV virus mutates to evade antiretroviral therapy (ART) drugs in infected people who have begun treatment. Drug-resistant HIV can spread from person to person, and people initially infected with drug-resistant HIV have drug resistance to one or more HIV medicines even before initiating ART.

From April 2009 to December 2014, the study enrolled 233 individuals with acute HIV infection, and researchers performed drug resistance testing before participants began ART. MHRP scientists and collaborators had previously found a 9.2% prevalence of TDR in a Thai cohort that included primarily MSM individuals with acute infection. The new analysis showed TDR prevalence declined to 4.8% in 2013 to 2014. 

Prevalence below 5% meets the World Health Organization’s definition of low-level TDR, for which routine resistance testing prior to treatment in the public health setting is not recommended.  In contrast, the U.S. and several Western countries are faced with higher TDR prevalence, and resistance testing prior to initiating ART is recommended to guide selection of first-line ART. 

The decline in TDR was most striking in resistance to NNRTI drugs, which showed a decrease from 9.4% to 0.7%. Resistance to NRTI drugs declined from 6.3% to 1.4%, while PI drug resistance had no discernible trend. 

“The low and declining rate of NNRTI resistance is reassuring, given that the current preferred first-line ART regimens in both the Thai and WHO HIV treatment guidelines contain the NNRTI efavirenz,” said Dr. Jintanat Ananworanich, MHRP’s Associate Director for Therapeutics Research and protocol chair of the RV254 acute infection cohort study in Thailand. 

Though the precise cause of the decline in TDR prevalence in the cohort is unknown, in recent years Thailand has changed the preferred regimen for HIV treatment to drugs that require less frequent dosing, have fewer side effects and are better tolerated by patients. “All of these characteristics have been associated with better treatment adherence, which is thought to contribute to decreased drug resistance,” explained Dr. Ananworanich.

Acute HIV infection presents the most opportune time to test for TDR. Previous research has shown that TDR is found at higher prevalence during the acute period than in chronically infected patients, and that resistance mutations detected early in HIV infection may eventually become undetectable in the absence of selective pressure from ART. 

MHRP’s RV254 acute infection cohort study focuses on the earliest stages of infection in order to understand what’s needed to create an effective HIV vaccine and possibly inform future investigations into a cure for HIV.